De La Barrera S S, Finiasz M, Frias A, Alemán M, Barrionuevo P, Fink S, Franco M C, Abbate E, del C Sasiain M
Departamento de Inmunología, Instituto de Investigaciones Hematológicas (IIHema), Academia Nacional de Medicina, Buenos Aires, Argentina.
Clin Exp Immunol. 2003 Jun;132(3):450-61. doi: 10.1046/j.1365-2249.2003.02176.x.
The ability of peripheral blood mononuclear cells (PBMC) from patients with active tuberculosis to display cytotoxic responses against autologous Mycobacterium tuberculosis (Mtb)-pulsed macrophages was evaluated. Non-MHC restricted cell-dependent lytic activity was observed in ex vivo effector cells from tuberculosis patients and was mediated mainly by CD3(+)gammadelta TCR(+) T (gammadelta T) cells bearing CD56 and/or CD16 molecules. MHC-restricted and non-MHC restricted cytotoxic T cells (CTL) were differentially expanded upon stimulation with Mtb in tuberculosis patients and normal controls (N). Class-I restricted CD8(+) CTL and class-II restricted CD4(+) CTL were generated in PPD(+)N and to a lesser extent in PPD(-)N. Mtb-stimulated effector cells from tuberculosis patients became progressively non-MHC restricted CD4(-)CD8(-)gammadelta T cells, while lytic activity of CD4(+) and CD8(+)CTL decreased gradually as the disease became more severe. On the other hand, target cells were lysed by ex vivo cells from tuberculosis patients through the Fas-FasL and perforin pathways. Mtb-induced CD4(+) CTL from tuberculosis patients and N controls preferentially employed the Fas-FasL mechanism. Mtb-induced CD8(+) CTL effector cells from patients used the perforin-based mechanism while cells from N controls also used the Fas-FasL pathway. While Mtb-induced gammadelta CTL from patients and PPD(-)N employed the latter mechanism cells from PPD(+)N individuals also used the perforin pathway. It can be concluded that shifts in the CTL response and the cytolytic mechanisms take place as the pulmonary involvement becomes more severe.
评估了活动性肺结核患者外周血单个核细胞（PBMC）对自体结核分枝杆菌（Mtb）脉冲巨噬细胞产生细胞毒性反应的能力。在结核病患者的体外效应细胞中观察到非MHC限制的细胞依赖性溶解活性，其主要由携带CD56和/或CD16分子的CD3(+)γδTCR(+)T（γδT）细胞介导。在结核病患者和正常对照（N）中，用Mtb刺激后，MHC限制和非MHC限制的细胞毒性T细胞（CTL）有不同程度的扩增。在PPD(+)N中产生了I类限制的CD8(+)CTL和II类限制的CD4(+)CTL，在PPD(-)N中产生的程度较小。来自结核病患者的Mtb刺激的效应细胞逐渐变为非MHC限制的CD4(-)CD8(-)γδT细胞，而随着疾病变得更严重，CD4(+)和CD8(+)CTL的溶解活性逐渐降低。另一方面，结核病患者的体外细胞通过Fas-FasL和穿孔素途径裂解靶细胞。来自结核病患者和N对照的Mtb诱导的CD4(+)CTL优先采用Fas-FasL机制。来自患者的Mtb诱导的CD8(+)CTL效应细胞使用基于穿孔素的机制，而来自N对照的细胞也使用Fas-FasL途径。虽然来自患者和PPD(-)N的Mtb诱导的γδCTL采用后一种机制，但来自PPD(+)N个体的细胞也使用穿孔素途径。可以得出结论，随着肺部受累变得更严重，CTL反应和细胞溶解机制会发生变化。
